During normal pregnancy, the fetus expresses many antigens that are foreign to the mother and could be recognized and attacked by the maternal immune system. However, several mechanisms ensure that allogeneic fetuses survive and flourish during normal pregnancy. The overall hypothesis is that the maternal immune system is selectively inhibited during pregnancy, to achieve the best compromise between resistance to disease versus fetal survival. In particular, a previously-developed model suggests that inflammatory Th1 and cytotoxic responses, which are harmful to the fetus, are selectively inhibited during pregnancy. This may protect the fetus, but also results in increased susceptibility to diseases that require Th1 or cytotoxic responses for their eradication. This model has been modified to reconcile reports of generalized and specific inhibition of immunity during pregnancy, with other studies suggesting that the mother can respond normally against paternal antigens. The new model proposes that strong but not weak Th1 or CD8 cytotoxic T cell responses are inhibited during pregnancy, so that the maternal immune response could still make effective Th1 responses against some pathogens, and would only be inhibited when the risk of fetal damage became significant. This model will be tested using T cell receptor transgenic T cells as tracer cells to analyze suppression induced by strong or weak immune responses during pregnancy. Immune responses will be varied by increasing the antigen amount, and by inducing simultaneous inflammation or infection. Potential non-specific or paternal antigen-specific suppression of Th1 immune responses will be tested. Possible diversion of T cells into other, less damaging effector phenotypes will also be examined. Finally, the role of Progesterone in suppressing the differentiation and activation of Th1 cells will be analyzed. A clearer understanding of alterations in maternal immunity may aid the design of vaccines for use during pregnancy, and may also lead to improved strategies for inhibiting autoimmunity.